1. Field of the Invention
The present invention relates to methods for preparing prenyl alcohol (3-methyl-2-buten-1-ol) and ester derivatives of prenyl alcohol. Prenyl alcohol is an intermediate in the manufacture of citral, a specialty chemical used in the flavor and fragrance industries, as well as in the manufacture of vitamins A and E, the anti-acne drugs Retin-A and Accutane.RTM., and several widely-used carotenoids, including beta-carotene.
One of the most expedient routes to citral (5) involves a thermal rearrangement of 3-methyl-1-(3-methyl-2-buten-1-oxy)-1,3-butadiene (4), which is readily obtained when acetal 3 prepared from prenyl alcohol, 2 and 3-methyl-2-butenal (prenal, 1)! is heated in the presence of a weak acid catalyst (e.g., acetic acid or 2,4-dinitrophenol) at temperatures in the range of 125.degree.-150.degree. C. The pathway by which unsaturated ether 4 is converted to citral (5) involves a Claisen rearrangement, followed by a subsequent Cope rearrangement in the same reaction vessel: ##STR1##
The approach to citral described above has been known for more than 25 years and has continued to be developed to the stage where one is able to effect the conversion of prenal (1) and prenyl alcohol (2) to citral (5) in a "one-pot" process. See, European patent application EP 344,043 (Nov. 29, 1989) filed by Rhone-Poulenc Chem. Abstracts 1990, 112, 179516d! and PCT Int. Appl. WO 91 09,830 (Jul. 11, 1991) Chem. Abstracts 1991, 115, 114815t!. Previous patents have verified that unsaturated ether 4 (obtained directly from acetal 3) can be converted to citral in high yield (90-100%), e.g.:
(a) German patent 2,411,530 (Sep. 26, 1974 to Hoffmann-LaRoche): Chem. Abstracts 1975, 82, 4434k. PA1 (b) U.S. Pat. No. 4,016,212 (Apr. 5, 1977 to Hoffmann-LaRoche): Chem. Abstracts 1977, 87, 136042u. PA1 (c) German patent 2,423,409 (Nov. 28, 1974 to Teijin Ltd. of Japan): Chem. Abstracts 1979, 91, 123406y. PA1 (d) German patent 2,625,074 (Dec. 8, 1977 to BASF): Chem. Abstracts 1978, 88, 89114c. PA1 (e) European patent application 21,074 (Jan. 7, 1981, filed by BASF): Chem. Abstracts 1981, 95, 7513q. PA1 (f) Japanese patent 61 22,038 issued to Kuraray Co., Ltd.: Chem. Abstracts 1986, 105, 134188n. PA1 a) By reacting chloroacetic acid with chlorine using a PCl.sub.3 catalyst; PA1 b) By reacting acetaldehyde with excess chlorine to form trichloroacetaldehyde--Cl.sub.3 CCHO. When dissolved in an aqueous mixture of calcium carbonate and sodium cyanide, and heated to about 85.degree. C., trichloroacetaldehyde can be converted to dichloroacetic acid; or PA1 c) Trichloroacetic acid can be electrolytically reduced to dichloroacetic acid. PA1 (a) An alkanoic acid, pk.sub.a (relative to water) &lt;4, in molar excess. Mixtures of such acids; or a concentrated solution (greater than 1 M) of such an acid in a weaker acid solvent (e.g., acetic or propionic acid) can also be used. However, for the stronger/weaker acid type of solvent system, the process is quite slow. PA1 (b) Slow addition of isoprene (e.g., dropwise addition over a period of several hours) to the alkanoic acid is required for a good yield. If isoprene is added in one portion, the prenyl cation (CH.sub.3).sub.2 C.dbd.CHCH.sub.2.sup..sym. ! generated by protonation of isoprene can react with another isoprene to give polymeric terpenes, rather than being trapped by RCO.sub.2 H or RCO.sub.2.sup..crclbar. to yield the desired prenyl ester (7). PA1 (c) The reaction occurs readily at room temperature; thus heating is not required. However, absent heating, the reaction proceeds very slowly when formic acid is employed (Example VI). PA1 (d) The presence of an organic base, (R'CO.sub.2).sub.x M, where M is a Group I or Group II cation and x is 1 or 2, is not necessary, but is desirable for optimizing yields of prenyl esters (7). R'CO.sub.2.sup..crclbar. is better at trapping the prenyl cation than is the carboxylic acid itself. The conjugate base (RCO.sub.2.sup.-) of the reactant carboxylic acid is preferred. However, other carboxylate bases can also be used. For example, the strongest base one can have in appreciable quantity in dichloroacetic acid is Cl.sub.2 CHCO.sub.2.sup..crclbar.. If one adds sodium acetate (a stronger base) to dichloroacetic acid, a reaction occurs to yield acetic acid (a weaker acid) and sodium dichloroacetate (a weaker base). Thus, the process can be conducted by using the "strong" carboxylic acid in excess (e.g., Cl.sub.2 CHCO.sub.2 H) and adding a salt of a weaker carboxylic acid (e.g., sodium propionate or potassium acetate) to generate the desired carboxylate anion (Cl.sub.2 CHCO.sub.2.sup.-) in situ.
The principal difficulty with the above process is the high cost of prenyl alcohol--which is almost as costly as citral. Once prenyl alcohol (2) is obtained, however, it can be conveniently oxidized with air in the presence of various metallic or metallic salt catalysts to yield the corresponding aldehyde prenal (1)!. Refer to: M. Matsumoto, et al., J. Org. Chem. 1984, 49, 3435, and Japanese patent 60 239,443 issued to Kuraray Co., Ltd. Chem. Abstracts 1986, 104, 148312q!.
2. Description of Related Art
Isoprene 2-methyl-1,3-butadiene, CH.sub.2 .dbd.C(CH.sub.3)CH.dbd.CH.sub.2 ! would seem to be a useful and potentially low-cost precursor to prenyl alcohol (2). Isoprene, which is used to make "synthetic natural rubber," can be obtained by "cracking" petroleum or--more conveniently--by a Prins reaction involving isobutylene and formaldehyde: ##STR2## See, Japanese patent 71 14,107, issued to Sumitomo Chemical Co., Ltd. Chem. Abstracts 1972, 77, 153520j!.
Unfortunately, acid-catalyzed addition of water to isoprene yields only a minor amount of prenyl alcohol and a substantial amount of the isomeric tertiary alcohol shown below: ##STR3## In addition to the above two alcohols, various other products are obtained in this reaction. Reference: Chem. Abstracts 1973, 78, 84547e.
Another approach to the formation of prenyl alcohol (2) from isoprene involves the addition of hydrohalic acids (HX: HCl or HBr) to isoprene. Although this reaction does yield prenyl halides (CH.sub.3).sub.2 C.dbd.CHCH.sub.2 X, X.dbd.Br or Cl!, yields are only moderate and the reaction is complicated by the fact that HX also adds to the double bond in the initially formed prenyl halide to give a dihalide: ##STR4## Furthermore, prenyl bromide (or chloride) is highly toxic, rather volatile, and decomposes if one attempts to distill it at atmospheric pressure. On the other hand, if one has prenyl halides (6) available, the following route to prenyl alcohol has been developed: ##STR5## Refer to: Japanese patent 77 10,207 issued to Kuraray Co., Ltd. Chem. Abstracts 1977, 87, 38852p! and German patent 3,021,414 (Dec. 11, 1980, issued to Montedison; Chem. Abstracts 1981, 94, 174311h).